Recent studies by Drs. S. Weiss and coworkers have shown that low frequency stimulation (LFS) of the amygdala blocks the development and expression of amygdala-kindled seizures produced by repeated application of a high frequency stimulus (Neuroreport 1995;6:2171-2176). In an effort to understand the underlying mechanisms, an amygdala slice preparation was developed in order to directly evaluate plasticity in the basal lateral nucleus of the amygdala. We record intracellular synaptic responses in the amygdala evoked by stimulation of the external capsule (EC) or stria terminalis (ST). We first attempted to establish the nature of this synaptic plasticity by using experimental protocols similar to those used to induce LTP or LTD in the hippocampus. High frequency stimulation (HFS, 100 Hz/1 S) of the EC or ST induced post- tetanic potentiation (PTP) lasting 1.4 +/- 0.4 min and short-term potentiation (STP) lasting 8.3 +/- 2.6 min. STP, but not PTP, was blocked by 100 muM APV, an NMDA receptor antagonist. LFS (1 Hz) of the ST or EC alone induced an enhancement (154 +/- 7%) in the amplitude of synaptic responses that was maintained for >30 min following termination of the stimulation. In contrast, when LFS was applied following recovery from the transient potentiating effect of HFS, there was a transient enhancement (126 +/- 4%) of the synaptic response followed by persistent synaptic depression (76 +/- 7% of baseline response). This depressed synaptic response could be potentiated by HFS. These studies demonstrate that LFS in the in vitro amygdaloid slice can depotentiate a facilitated synaptic response.